tbuckley/cabot-search huggingface dataset:
Loss of phospholipase PLAAT3 causes a mixed lipodystrophic and neurological syndrome due to impaired PPARγ signaling
Authors: Nika Schuermans, Salima El Chehadeh, Dimitri Hemelsoet, Jérémie Gautheron, Marie-Christine Vantyghem, Sonia Nouioua, Meriem Tazir, Corinne Vigouroux, Martine Auclair, Elke Bogaert, Sara Dufour, Fumiya Okawa, Pascale Hilbert, Nike Van Doninck, Marie-Caroline Taquet, Toon Rosseel, Griet De Clercq, Elke Debackere, Carole Van Haverbeke, Ferroudja Ramdane Cherif, Jon Andoni Urtizberea, Jean-Baptiste Chanson, Benoit Funalot, François-Jérôme Authier, Sabine Kaya, Wim Terryn, Steven Callens, Bernard Depypere, Jo Van Dorpe, Arnaud V. Vanlander, Patrick Verloo, Paul J. Coucke, Bruce Poppe, Francis Impens, Noboru Mizushima, Christel Depienne, Isabelle Jéru, Bart Dermaut
Journal: Nature Genetics (2023)
Multiple-instance learning of somatic mutations for the classification of tumour type and the prediction of microsatellite status
Authors: Jordan Anaya, John-William Sidhom, Faisal Mahmood, Alexander S. Baras
Journal: Nature Biomedical Engineering (2023)

Large-scale genomic data are well suited to analysis by deep learning algorithms. However, for many genomic datasets, labels are at the level of the sample rather than for individual genomic measures. Machine learning models leveraging these datasets generate predictions by using statically encoded measures that are then aggregated at the sample level. Here we show that a single weakly supervised end-to-end multiple-instance-learning model with multi-headed attention can be trained to encode and aggregate the local sequence context or genomic position of somatic mutations, hence allowing for the modelling of the importance of individual measures for sample-level classification and thus providing enhanced explainability. The model solves synthetic tasks that conventional models fail at, and achieves best-in-class performance for the classification of tumour type and for predicting microsatellite status. By improving the performance of tasks that require aggregate information from genomic datasets, multiple-instance deep learning may generate biological insight.
scDiffCom: a tool for differential analysis of cell–cell interactions provides a mouse atlas of aging changes in intercellular communication
Authors: Cyril Lagger, Eugen Ursu, Anaïs Equey, Roberto A. Avelar, Angela Oliveira Pisco, Robi Tacutu, João Pedro de Magalhães
Journal: Nature Aging (2023)

Dysregulation of intercellular communication is a hallmark of aging. To better quantify and explore changes in intercellular communication, we present scDiffCom and scAgeCom. scDiffCom is an R package, relying on approximately 5,000 curated ligand-receptor interactions, that performs differential intercellular communication analysis between two conditions from single-cell transcriptomics data. Built upon scDiffCom, scAgeCom is an atlas of age-related cell-cell communication changes covering 23 mouse tissues from 58 single-cell RNA sequencing datasets from Tabula Muris Senis and the Calico murine aging cell atlas. It offers a comprehensive resource of tissue-specific and sex-specific aging dysregulations and highlights age-related intercellular communication changes widespread across the whole body, such as the upregulation of immune system processes and inflammation, the downregulation of developmental processes, angiogenesis and extracellular matrix organization and the deregulation of lipid metabolism. Our analysis emphasizes the relevance of the specific ligands, receptors and cell types regulating these processes. The atlas is available online ( https://scagecom.org ).
High-Efficiency Particulate Air Filters for Preventing Wildfire-related Asthma Complications: A Cost-Effectiveness Study
Authors: Amin Adibi, Prabjit Barn, Erin M. Shellington, Stephanie Harvard, Kate M. Johnson, Christopher Carlsten
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Air pollution caused by wildfire smoke is linked to adverse health outcomes, especially for people living with asthma.
Antitumor Activity and Safety of Dostarlimab Monotherapy in Patients With Mismatch Repair Deficient Solid Tumors
Authors: Thierry André, Dominique Berton, Giuseppe Curigliano, Renaud Sabatier, Anna V. Tinker, Ana Oaknin, Susan Ellard, Filippo de Braud, Hendrik-Tobias Arkenau, José Trigo, Adriano Gravina, Rebecca Kristeleit, Victor Moreno, Cyril Abdeddaim, Yann-Alexandre Vano, Vanessa Samouëlian, Rowan Miller, Valentina Boni, Antonio Antón Torres, Lucy Gilbert, Jubilee Brown, Ninad Dewal, Christine Dabrowski, Grace Antony, Eleftherios Zografos, Jennifer Veneris, Susana Banerjee
Journal: JAMA Network Open (2023)

Mismatch repair deficiency (dMMR) occurs in various cancers, and these tumors are attractive candidates for anti-programmed cell death 1 therapies, such as dostarlimab, a recently approved immune checkpoint inhibitor.
Cost-Effectiveness Analysis of Myopia Progression Interventions in Children
Authors: Sylvia Agyekum, Poemen P. Chan, Prince E. Adjei, Yuzhou Zhang, Zhaohua Huo, Benjamin H. K. Yip, Patrick Ip, Ian C. K. Wong, Wei Zhang, Clement C. Tham, Li Jia Chen, Xiu Juan Zhang, Chi Pui Pang, Jason C. Yam
Journal: JAMA Network Open (2023)

Several interventions exist for treating myopia progression in children. While these interventions' efficacy has been studied, their cost-effectiveness remains unknown and has not been compared.
Racial Disparities in Candidates for Hepatocellular Carcinoma Liver Transplant After 6-Month Wait Policy Change
Authors: Behnam Saberi, Ahmet Gurakar, Hani Tamim, Carolin V. Schneider, Omar T. Sims, Alan Bonder, Zachary Fricker, Saleh A. Alqahtani
Journal: JAMA Network Open (2023)

Importance Racial disparities in liver transplant (LT) for hepatocellular carcinoma (HCC) may be associated with unequal access to life-saving treatment. Objective To quantify racial disparities in LT for HCC and mortality after LT, adjusting for demographic, clinical, and socioeconomic factors. Design, Setting, and Participants This cohort study was a retrospective analysis of United Network Organ Sharing/Organ Procurement Transplant Network (OPTN) data from 2003 to 2021. Participants were adult patients with HCC on the LT waiting list and those who received LT. Data were analyzed from March 2022 to September 2023. Exposures Race and time before and after the 2015 OPTN policy change. Main Outcomes and Measures Proportion of LT from wait-listed candidates, the proportion of waiting list removals, and mortality after LT. Results Among 12 031 patients wait-listed for LT with HCC (mean [SD] age, 60.8 [7.4] years; 9054 [75.3%] male; 7234 [60.1%] White, 2590 [21.5%] Latinx/o/a, and 1172 [9.7%] Black or African American), this study found that after the 2015 model of end-stage liver disease (MELD) exception policy changes for HCC (era 2), the overall proportion of LT for HCC across all races decreased while the proportion of dropouts on the LT waiting list remained steady compared with patients who did not have HCC. In Kaplan-Meier analysis, Asian patients demonstrated the lowest dropout rates in both era 1 and era 2 (1-year dropout, 16% and 17%, respectively; P &amp;amp;lt; .001). In contrast, Black or African American patients had the highest dropout rates in era 1 (1-year dropout, 24%), but comparable dropout rates (23%) with White patients (23%) and Latinx/o/a patients in era 2 (23%). In both eras, Asian patients had the highest survival after LT (5-year survival, 82% for era 1 and 86% for era 2), while Black or African American patients had the worst survival after LT (5-year survival, 71% for era 1 and 79% for era 2). In the multivariable analysis for HCC LT recipients, Black or African American race was associated with increased risk of mortality in both eras, compared with White race (HR for era 1, 1.17; 95% CI, 1.05-1.35; and HR for era 2, 1.31; 95% CI, 1.10-1.56). Conclusions and Relevance This cohort study of LT candidates in the US found that after the 2015 MELD exception policy change for HCC, the proportion of LT for HCC had decreased for all races. Black or African American patients had worse outcomes after LT than other races. Further research is needed to identify the underlying causes of this disparity and develop strategies to improve outcomes for HCC LT candidates.
Tom Nolan’s research reviews—2 November 2023
Authors: Tom Nolan
Journal: BMJ (2023)

Thyroid over-suppression and cognitive disordersHow much should we worry about over-suppression of thyroid simulating hormone (TSH) when reviewing blood results in older people being treated for hypothyroidism?A cohort study looked at the records of over 60 000 patients in the US with thyrotoxicosis, defined as a TSH level below reference range.It found that patients with exogenous thyrotoxicosis-due to overtreatment of hypothyroidism-were more likely to receive a cognitive disorder diagnosis by the age of 75 years (adjusted hazard ratio 1.34 (95% confidence interval 1.10 to 1.63).The risk was greater for those with TSH ≤0.1 mIU/L.This observational study can't prove causality, but it is enough to remind us that a low TSH level in an older person being treated for hypothyroidism should prompt a medication review.
Clinical Features vs CT Findings to Estimate Need for Surgery in Small Bowel Obstruction
Authors: Sara Schulwolf, Charles Brower, Alessandra Karam, Joaquim Havens, Hamid Shokoohi, Nicole M. Duggan, Andrew J. Goldsmith
Journal: JAMA Network Open (2023)

This comparative effectiveness research compares the ability of clinical features vs clinical features with computed tomography (CT) to estimate the need for small bowel obstruction surgery.
Electronic Nicotine Delivery Systems and E-Liquid Modifications to Vape Cannabis Depicted in Online Videos
Authors: Rachel R. Ouellette, Sophia Selino, Grace Kong
Journal: JAMA Network Open (2023)

Electronic nicotine delivery systems (ENDS) were created to vape nicotine e-liquids; however, social media demonstrates increased ENDS modifications to vape cannabis. Analysis of social media content helps with understanding ENDS modifications for cannabis use, overlapping markets for ENDS and cannabis, and the need for additional regulation.
<i>Streptococcus salivarius</i> Probiotics to Prevent Acute Otitis Media in Children
Authors: Suvi Sarlin, Ulla Koskela, Minna Honkila, Paula A. Tähtinen, Tytti Pokka, Marjo Renko, Terhi Tapiainen
Journal: JAMA Network Open (2023)

New approaches for the prevention of acute otitis media (AOM), the most common reason for antibiotic use in children, are needed.
Vaginal Estrogen Therapy Use and Survival in Females With Breast Cancer
Authors: Lauren McVicker, Alexander M. Labeit, Carol A. C. Coupland, Blánaid Hicks, Carmel Hughes, Úna McMenamin, Stuart A. McIntosh, Peter Murchie, Chris R. Cardwell
Journal: JAMA Oncology (2023)

Genitourinary syndrome of menopause can be treated with vaginal estrogen therapy. However, there are concerns about the safety of vaginal estrogen therapy in patients with breast cancer.
Notice of Retraction: Worthington MA et al. Dynamic Prediction of Outcomes for Youth at Clinical High Risk for Psychosis: A Joint Modeling Approach. <i>JAMA Psychiatry.</i> 2023;80(10):1017-1025.
Authors: Tyrone D. Cannon, Michelle A. Worthington, Jean Addington, Carrie E. Bearden, Kristin S. Cadenhead, Barbara A. Cornblatt, Matcheri Keshavan, Cole A. Lympus, Daniel H. Mathalon, Diana O. Perkins, William S. Stone, Elaine F. Walker, Scott W. Woods, Yize Zhao
Journal: JAMA Psychiatry (2023)

To the Editor In consulting with another group attempting to replicate our analyses, we have identified a coding error in the joint modeling analyses in our article, "Dynamic Prediction of Outcomes for Youth at Clinical High Risk for Psychosis: A Joint Modeling Approach," 1 published online on August 2, 2023, and in the October 2023 issue of JAMA Psychiatry.Specifically, the converter by time interaction term used in the feature selection phase of the longitudinal mixed-effects analyses was mistakenly retained in the longitudinal mixed-effects component of the joint models, but only the time effect should have been used in this phase.As a result of this error, the short-term longitudinal features used to boost performance of the baseline prediction models contained information on the outcomes to be predicted, making them not about prediction per se but about describing differential change as a function of outcome.The results for the base models and the feature selection stage are correct, but the results for the joint models that combine the base models and the selected longitudinal features are subject to this error.When the joint model analyses were rerun with the correct coding, they no longer showed improved prediction accuracy over and above the performance of the Cox regression models incorporating baseline-only predictors.Because the primary significance and novelty of the article were based on improved prediction in joint models incorporating information on short-term clinical change, we have requested that the article be retracted.Until studies of new samples are completed, short-term (baseline to 2-month) clinical change cannot be used to boost the performance of baseline-only prediction models of psychosis and remission of clinical high-risk status.We apologize for any confusion this error may have caused.
Exclusion of Ranitidine From Premedication Regimens During Paclitaxel Treatment
Authors: Daan W. Huntjens, Joost W. Vanhommerig, Willem van de Veen, Mirjam Crul
Journal: JAMA Oncology (2023)

This cohort study conducted in the Netherlands uses electronic medical records to assess incidence of hypersensitivity reactions with and without H2-receptor antagonist premedication before paclitaxel administration.
Racial Disparities and Survival Outcomes in Breast Cancer
Authors: Haruki Shigeta, Akihiko Ozaki, Tetsuya Tanimoto
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
In situ vaccination via tissue-targeted cDC1 expansion enhances the immunogenicity of chemoradiation and immunotherapy
Authors: Brandon Lam, Yu Jui Kung, John Lin, Ssu-Hsueh Tseng, Hsin-Fang Tu, Claire Huang, Brandon Lee, Esteban Velarde, Ya Chea Tsai, Rafael Villasmil, Sung Taek Park, Deyin Xing, Chien-Fu Hung, T.-C. Wu
Journal: Journal of Clinical Investigation (2023)

Even with the prolific clinical use of next-generation cancer therapeutics, many tumors remain unresponsive or become refractory to therapy, creating a medical need. In cancer, DCs are indispensable for T cell activation, so there is a restriction on cytotoxic T cell immunity if DCs are not present in sufficient numbers in the tumor and draining lymph nodes to take up and present relevant cancer antigens. To address this bottleneck, we developed a therapeutic based on albumin fused with FMS-related tyrosine kinase 3 ligand (Alb-Flt3L) that demonstrated superior pharmacokinetic properties compared with Flt3L, including significantly longer half-life, accumulation in tumors and lymph nodes, and cross-presenting-DC expansion following a single injection. We demonstrated that Alb-Flt3L, in combination with standard-of-care chemotherapy and radiation therapy, serves as an in situ vaccination strategy capable of engendering polyclonal tumor neoantigen-specific immunity spontaneously. In addition, Alb-Flt3L-mediated tumor control synergized with immune checkpoint blockade delivered as anti-PD-L1. The mechanism of action of Alb-Flt3L treatment revealed a dependency on Batf3, type I IFNs, and plasmacytoid DCs. Finally, the ability of Alb-Flt3L to expand human DCs was explored in humanized mice. We observed significant expansion of human cross-presenting-DC subsets, supporting the notion that Alb-Flt3L could be used clinically to modulate human DC populations in future cancer therapeutic regimens.
Breast Cancer Incidence After a False-Positive Mammography Result
Authors: Xinhe Mao, Wei He, Keith Humphreys, Mikael Eriksson, Natalie Holowko, Haomin Yang, José Tapia, Per Hall, Kamila Czene
Journal: JAMA Oncology (2023)

False-positive mammography results are common. However, long-term outcomes after a false-positive result remain unclear.
Racial Disparities and Survival Outcomes in Breast Cancer—Reply
Authors: Kent F. Hoskins, Garth H. Rauscher
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
CDKL5 regulates p62-mediated selective autophagy and confers protection against neurotropic viruses
Authors: Josephine W. Thinwa, Zhongju Zou, Emily Parks, Salwa Sebti, Kelvin Hui, Yongjie Wei, Mohammad Goodarzi, Vibha Singh, Greg Urquhart, Jenna L. Jewell, Julie K. Pfeiffer, Beth Levine, Tiffany A. Reese, Michael U. Shiloh
Journal: Journal of Clinical Investigation (2023)

Virophagy, the selective autophagosomal engulfment and lysosomal degradation of viral components, is crucial for neuronal cell survival and antiviral immunity. However, the mechanisms leading to viral antigen recognition and capture by autophagic machinery remain poorly understood. Here, we identified cyclin-dependent kinase-like 5 (CDKL5), known to function in neurodevelopment, as an essential regulator of virophagy. Loss of function mutations in CDKL5 are associated with a severe neurodevelopmental encephalopathy. We found deletion of CDKL5 or expression of a clinically-relevant pathogenic mutant of CDKL5 reduced virophagy of Sindbis virus (SINV), a neurotropic RNA virus, and increased intracellular accumulation of SINV capsid protein aggregates and cellular cytotoxicity. CDKL5 knockout mice displayed increased viral antigen accumulation and neuronal cell death after SINV infection and enhanced lethality after infection with several neurotropic viruses. Mechanistic studies demonstrated that CDKL5 directly binds the canonical selective autophagy receptor p62 and phosphorylates p62 at T269/S272 to promote its interaction with viral capsid aggregates. We found that CDKL5-mediated phosphorylation of p62 facilitated the formation of large p62 inclusion bodies that captured viral capsids to initiate capsid targeting to autophagic machinery. Overall, these findings identify a cell-autonomous innate immune mechanism for autophagy activation to clear intracellular toxic viral protein aggregates during infection.
A red and watering eye
Authors: Koushik Tripathy, Aneesha M Ichlangod, Uma Sridhar, Milap Vaghela
Journal: BMJ (2023)

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Increased expression of CXCL6 in secretory cells drives fibroblast collagen synthesis and is associated with increased mortality in idiopathic pulmonary fibrosis
Authors: Harinath Bahudhanapati, Jiangning Tan, Rosa Marie Apel, Benjamin Seeliger, Jonas Schupp, Xiaoyun Li, Daniel I. Sullivan, John Sembrat, Mauricio Rojas, Tracy Tabib, Eleanor Valenzi, Robert Lafyatis, Nilay Mitash, Ricardo Hernandez Pineda, Chetan Jawale, Doureradjou Peroumal, Partha Biswas, John Tedrow, Taylor Adams, Naftali Kaminski, Wim A. Wuyts, John F. McDyer, Kevin F. Gibson, Jonathan K. Alder, Melanie Königshoff, Yingze Zhang, Mehdi Nouraie, Antje Prasse, Daniel J. Kass
Journal: European Respiratory Journal (2023)

Rationale Recent data suggest that the localisation of airway epithelial cells in the distal lung in idiopathic pulmonary fibrosis (IPF) may drive pathology. We set out to discover whether chemokines expressed in these ectopic airway epithelial cells may contribute to the pathogenesis of IPF. Methods We analysed whole lung and single-cell transcriptomic data obtained from patients with IPF. In addition, we measured chemokine levels in blood, bronchoalveolar lavage (BAL) of IPF patients and air–liquid interface cultures. We employed ex vivo donor and IPF lung fibroblasts and an animal model of pulmonary fibrosis to test the effects of chemokine signalling on fibroblast function. Results By analysis of whole-lung transcriptomics, protein and BAL, we discovered that CXCL6 (a member of the interleukin-8 family) was increased in patients with IPF. Elevated CXCL6 levels in the BAL of two cohorts of patients with IPF were associated with poor survival (hazard ratio of death or progression 1.89, 95% CI 1.16–3.08; n=179, p=0.01). By immunostaining and single-cell RNA sequencing, CXCL6 was detected in secretory cells. Administration of mCXCL5 (LIX, murine CXCL6 homologue) to mice increased collagen synthesis with and without bleomycin. CXCL6 increased collagen I levels in donor and IPF fibroblasts 4.4-fold and 1.7-fold, respectively. Both silencing of and chemical inhibition of CXCR1/2 blocked the effects of CXCL6 on collagen, while overexpression of CXCR2 increased collagen I levels 4.5-fold in IPF fibroblasts. Conclusions CXCL6 is expressed in ectopic airway epithelial cells. Elevated levels of CXCL6 are associated with IPF mortality. CXCL6-driven collagen synthesis represents a functional consequence of ectopic localisation of airway epithelial cells in IPF.